Double-Blind, Placebo-Controlled, Randomized Study

Comparing 0.0003%Calcitriol with 0.1%Tacrolimus Ointments

for the Treatment of Endemic Pityriasis Alba

BereniceMoreno-Cruz, Bertha Torres-A'lvarez,Diana Hern'andez-Blanco, dan Juan Pablo Castanedo-Cazares

Dermatologi Departemen, Rumah Sakit Pusat "Dr. Ignacio Morones Prieto ", Universidad de San Luis Aut'onoma Potos'ı,

Avenida Carranza No. 2395, CP 78210, San Luis Potosi, Meksiko

Dr. Resati Nando Panonsih Sp. KK

By : Nurlaila ZuhriaYessica Fianita

Background

Pityriasis alba (PA) is a frequent cause of consultation in tropical areas due to its chronic course, frequent relapses, and notorious

hypopigmented lesions in pediatric dark skin populations. Currently, no

treatment is widely accepted

Introduction

There are two types of PA

(Pitiriasis Alba)

The endemic: affecting infants and children of low social

economic conditions in developing countries

Atopic dermatitis ; related PA which is

associated with postinflammatory hypopigmentation

It is characterized PA Hypopigmented, Irregular plaques

with well- to ill- defined borders,

Covered occasionally by fine scales; it affects mainly face, limbs, and sometimes thorax.

Etiologi and Risk factor

Its etiology is still unknown, Sun exposure is considered an involved

factor

Treatment:

Includes topical application of humectants, Corticosteroids, Sunscreens, Antiseptics, Immunosuppressors ( tacrolimus, pimecrolimus)

Have shown an excellent response in atopic related PA

Calcitriol (1,25-dihydroxyvitamin D3) is an endogenous hormonally-active derivative of vit D

Key words

Placebo

Ointments of 0.1% tacrolimus,

0.0003% calcitriol

The treatment of endemic

PA.

To assess the efficacy of 0.0003% calcitriol and 0.1% tacrolimus ointments compared with placebo in the treatment of endemic

PA.

Objective

Inklusi Registered at the US National Institutes

of Health Clinical Trial Register Patients from both genders, between 2-18

years old By symmetrical lesions of PA on the face,

between 2-6cm2

EksklusiWho had used any systemic or topical

medication during the past 6 weeks

Methods The investigation was an 8-week,

randomized, double-blind, split-face placebo-controlled trial.

The study was conducted at the Dermatology department of the Hospital Central of San Luis Potos´ı, M´exico

Twenty-eight children aged 3–17 years with 56 symmetrical lesions and phototype IV-V,

- Patients were examined at 2, 4, 6 and 8 weeks.- The primary outcome measure was the reduction of

the affected area.

- Imporvement Evaluated by :- Digital quantification of the affected area,

- Colorimetry, - Transepidermal water loss (TEWL)

- 0.0003% calcitrioL- 0.1% tacrolimus or - placebo (petrolatum

patients were

randomly assigned in a double-blind manner to

receive

To apply the treatment twice daily

Table 1. Demograpics, and clinical features of the 28 patients at baseline

Age (years), mean (SD) 10 (3.6)

Gender, n (%) Male Female

15 (54)13 (46)

Phototype IV v

7 (25)21 (75)

Duration of PA (months)Mean (SD) 9.6 (10.6)

Previous treatment, n (%) 10 (38)

Target lesions Area (cm²), mean (SD) L* axis, mean (SD) a* axis, mean (SD) TEWL (g/m²/h), mean (SD)

3.9 (1.3)56.7 (2.7)11.7 (1.5)14.9 (5)

Permuted block randomization was used to assign treatments on lesions.

Statistical analysis was : - Analysis of variance,

- Paired t test, - χ2 test (Fisher if n < 5)- Correlation tests

Tests were performed using the JMP software 8.0

Figure 1: Mean percentage change in the depigmented area of PA target lesions during the study for calcitriol (n = 19), tacrolimus (n = 18), and placebo (n = 19). At 8 weeks, there were differences among groups (one-way ANOVA, P < 0.001), but no difference was noted between calcitriol and tacrolimus (t test, P = 0.9).

Results

Tacrolimus and calcitriol ointments induced a mean improvement of 68%, compared to 44% of placebo.

We found an elevated TEWL in PA lesions. In the treated plaques, the reduction of the affected area was associated with improvement of pigmentation and TEWL

Figure 2: Physician’s assessment of response at PA target lesions at the end of treatment (week 8). Calcitriol and tacrolimus efficacy was rated equally for good and excellent response (P = 0.6, and P = 0.8, χ2 test). Placebo response was significantly lower compared to both drugs in the former categories (P < 0.001, χ2 test).

diskussion

This suggests that PA may have a local skin barrier defect◦ that may be associated to sebaceous glands

atrophy ◦lipids deficiency

which may contribute to the long duration and frequent relapses

Diskussion

Another significant fact is that we neither indicated sunscreen use, nor influenced sun exposure habits but we observed notorious improvement◦ this suggests that most important factors other than

UV radiation might be involved in the pathogenesis of this condition. These results made uswonder if steroids or immunosuppressors are justified forthis disease, besides considering its reported adverse effects

(i.e., cutaneous atrophy, carcinogenic risk, or infections)

Figure 3: PA lesion treated with 0.0003 % calcitriol in a 10-year-old girl, view at onset (left) and 8 weeks later (right). In the lower picture,target lesion was outlined to measure the affected area showing the excellent clinical response.Figure

Discussion

Figure 4: PA lesion treated with 0.1% tacrolimus ointment in a 7-year-old boy: onset and 8 weeks later with excellent improvement.

Table 2: Changes in repigmented area (%), colorimetric values (L∗, a∗), and TEWL (g/m2/h) on target lesions of PA. Data are shown

initially, and at the end of study for calcitriol, tacrolimus and placebo0.0003% Calcitriol

(n = 19)0.1% Tacrolimus

(n = 18)Placebo (n = 19)

Onset 8weeks

P Onset 8 week

s

P Onset 8 week

s

P

Reduced area (%)

0 68,2 (24,7

)

<0,001

0 69,1 (25,1

)

<0,001

0 47,6 (28,9

)

<0,001

L∗Δ 42 (4,3)

1,3 (1,9)

0,001 4,1 (1,1)

1,8 (1,2 )

0,001 4,3 (2,8)

2,7 (2,2)

0,09

a∗ Δ -0,4(1,

4)

0,1 (2,1)

0,35 -0,5 (1,5)

-0,3 (1,1)

0,65 0,4 (1,1)

-0,2 (2,6)

0,09

TEWL Δ

4,8(4,3)

1,6 (1,3)

0,008 4 (4,7)

1,7 (1)

0,65 4 (4,1)

3,5 0,63

Conclusions.

Calcitriol and tacrolimus induced similar repigmentation in endemic PA lesions. Melanogenic, anti-inflammatory, and barrier defect restoration properties of these drugs may explain these findings.

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